Henry Box Brown was born a slave in 1815 on a tobacco farm in Louisa County, Virginia, forty–five miles from Richmond. In The Narrative of the Life of Henry "Box" Brown, Written by Himself (1851), Brown describes his experience in slavery as comparatively mild from the standpoint of his physical treatment. Emotionally, however, it was extremely punishing at the hands of "tyrants and avaricious men, whose cold hearts cannot sympathise with your feelings." Brown's first realization of just how cruel slaveholders could be, came at the age of 15 when his family was divided up in an estate sale after the death of his master. Brown was sent to Richmond, Virginia, where his new master, William Barret, put Brown to work in Barret's tobacco factory.

Brown shared much in common with urban slaves, many of whom were allowed an unusual amount of freedom and autonomy. He lived apart from his owner in a boarding house run by Barret's free black overseer. Although Brown paid his master a portion of his wages, he was able to accumulate a significant sum of money. Brown explains in his narrative that he got the idea that if he were free, he could work as a tobacconist, because of his familiarity with the product. At the age of 21, Brown received his owner's permission to marry an enslaved woman who was owned by a bank clerk. William and Nancy Brown rented a house in Richmond where they began to raise their family. Like other enslaved husbands and fathers, Brown lived with the constant anxiety that his family could be sold at any time.

Brown's worst fear came to pass in August 1848 when his wife's owner suddenly sold her and their three children while Brown was at work. In one of the most heart–rending passages in all slave narratives, Brown describes seeing his family marched "with ropes around their necks and staples on their arms" through the streets of Richmond, to be sold to North Carolina: "[W]hat should I now see in the very foremost wagon but a little child looking towards me and pitifully calling, father! father! This was my eldest child, and I was obliged to look upon it for the last time that I should, perhaps, ever see it again in life." The sale of his family convinced Brown that, though he had been taught that resisting slavery was sinful, God would not punish him if he tried to escape his enslavement. He explained in his narrative that he was "willing to dare even death itself rather than endure any longer the clanking of those galling chains." His escape from slavery on March 29, 1849, was one of the most sensational ever recorded in fugitive slave accounts. Brown engaged a local shopkeeper and other white abolitionist friends to box him up in a shipping crate "three feet one inch wide, two feet six inches high, and two feet wide" and send him "conveyed like dry goods" from Richmond to Philadelphia. The trip took twenty–seven agonizing hours, several of which Brown spent upside down, enduring great pressure on his head. He believed he would surely die, but he survived to be greeted and welcomed by abolitionists at the antislavery office in Philadelphia, where his box was delivered. Within months of his arrival in the North, Brown became a celebrated speaker on the abolitionist circuit. After the Fugitive Slave Act was passed in 1850, Brown's notoriety made him a ready target for slave catchers, which forced him to move to England, where he married and continued to make public appearances as an antislavery lecturer throughout the 1850s.